Associations between blood cholinesterase activity and postoperative basal forebrain cholinergic system atrophy: Results from the BioCog cohort study

Sep 4, 2026

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Associations between blood cholinesterase activity and postoperative atrophy of cholinergic nuclei in the basal forebrain are investigated using data from the BioCog cohort. The study tests whether perioperative changes in cholinesterase activity relate to postoperative atrophy of the nucleus basalis of Meynert, and evaluates potential links to postoperative delirium and cognitive dysfunction. In a subsample of cognitively healthy older adults, lower postoperative butyryl-ChE activity corresponds to lower baseline-adjusted NBM volume, driven by perioperative change rather than preoperative levels.

LanguageEnglish

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Pages31

Reading Time11 min

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OBJECTIVE

METHODS

RESULTS

DISCUSSION

Introduction

medRxiv preprint doi: [https://doi.org/10.1101/2025.09.05.25335162](https://doi.org/10.1101/2025.09.05.25335162); this version posted September 7, 2025. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Associations between blood cholinesterase activity and postoperative basal forebrain cholinergic system atrophy: Results 5 from the BioCog cohort study Florian Lammers-Lietz* ,1 (0000-0002-7371-3947, [florian.lammers@charite.de](florian.lammers@charite.de)), Maria Heinrich1,2 (0000-0002-4530-7343, [maria.heinrich@charite.de](maria.heinrich@charite.de)), Kai Kappert 3 (0000-0001- 6976-0428, [kai.kappert@charite.de](kai.kappert@charite.de)), Georg Winterer 1,2 (0000-0002-3610-5029, 10 [georg.winterer@pi-pharmaimage.com](georg.winterer@pi-pharmaimage.com) ), Claudia Spies1 (0000-0002-1062-0495, [claudia.spies@charite.de](claudia.spies@charite.de)), Anika Müller 1 (0000-0002-6859-7080, [anika.mueller@charite.de](anika.mueller@charite.de)) 1 Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Anesthesiology and Intensive Care 15 Medicine | CCM | CVK, Augustenburger Platz 1, 13353 Berlin, Germany 2 PharmaImage Biomarker Solutions GmbH, Berlin, Germany 3 Charité – Universitätsmedizin Berlin, corporate Member of Freie Universität and Humboldt-Universität zu Berlin, Institute of Diagnostic Laboratory Medicine, Clinical Chemistry, and Pathobiochemistry, Berlin, Germany. 20 25 * Corresponding author: Florian Lammers-Lietz Charité – Universitätsmedizin Berlin, Department of Anesthesiology and Intensive Care Medicine | CCM | CVK Augustenburger Platz 1 (internal address: Mittelallee 3), 13353 Berlin, Germany e-mail: [florian.lammers@charite.de](florian.lammers@charite.de) , phone: ++49 30 450 651 458 NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: [https://doi.org/10.1101/2025.09.05.25335162](https://doi.org/10.1101/2025.09.05.25335162); this version posted September 7, 2025. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 30 OBJECTIVE: Structural and functional metabolism are closely linked in the cholinergic system, and associations between cholinergic neurotransmission and atrophy of cholinergic nuclei, i.e. , the nucleus basalis of Meynert (NBM), have been described for neurodegenerative conditions. Perioperative drug administration significantly impacts cholinergic neurotransmission, as shown by alterations in cholinesterase (ChE) activity of 35 patients undergoing anaesthesia and may contribute to perioperative disorders of cognition. In this work, we hypothesised that there is an association between perioperative ChE activity and postoperative NBM atrophy and studied its potential role in postoperative delirium (POD) and cognitive dysfunction (POCD) . METHODS: We studied a subsample from the BioCog cohort study. N=170 cognitively 40 healthy (MMSE≥24) patients ≥65 years provided blood samples for ChE activity measurement before elective surgery and on the first postoperative day, as well as magnetic resonance imaging data before surgery and at follow-up three months after surgery for volumetry of the NBM. Patients were screened for delirium until the 7th postoperative day. POCD was assessed three months after surgery and was defined according to the reliable 45 change index. The data were analysed in linear regression models of postoperative NBM volume adjusted for age, sex, MMSE score and preoperative NBM volum

FAQs

What is the study objective regarding cholinesterase activity and brain atrophy?

The study examines whether perioperative cholinesterase (ChE) activity is associated with postoperative atrophy of the nucleus basalis of Meynert (NBM) and whether this relates to postoperative delirium and cognitive dysfunction.

How were patients selected and what measurements were taken?

A BioCog subsample of cognitively healthy older adults provided blood for ChE activity before surgery and on the first postoperative day, and MRI data were collected before surgery and at three-month follow-up to measure NBM volume. Delirium was assessed until day 7, and POCD was assessed three months after surgery.

What were the key results and how did they relate to delirium or POCD?

Lower postoperative butyryl-ChE activity was associated with lower baseline-adjusted NBM volume, driven by perioperative change rather than preoperative activity. NBM volumes and ChE-NBM associations were not altered by POD or POCD status.

Sep 4, 2026

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